We propose to study the in vitro interaction of several amino acids with melphalan in human bone marrow cells and multiple myeloma cells. Melphalan is transported into L1210 leukemia cells and probably murine bone marrow precursor cells by the neutral amino acid transport systems. Previous studies have demonstrated that certain amino acids such as leucine and glutamine can diminish the in vitro cytotoxicity of melphalan in these cells, apparently secondary to a decreased intracellular concentration of the drug. The following in vitro experiments will be done. (a) We will determine dose response curves for melphalan alone in colony forming systems with human bone marrow cells (CFU-C) and myeloma cells. Various concentrations of melphalan and each amino acid will be employed in experiments to determine the ability of each amino acid to modify the cytotoxicity of this agent. (b) We will determine the effect of amino acids on the transport of melphalan into these cells by measuring the intracellular concentration of the drug at various time-points in the presence or absence of each amino acid. (c) We will describe the quantity of melphalan alkylation of DNA, RNA, and protein in the presence or absence of each amino acid that demonstrates significant inhibition of transport and cytotoxicity of this agent. Amino acids will be sought which inhibit the transport, alkylation and cytotoxicity of melphalan to a greater extent in human bone marrow cells as compared to myeloma cells.